1. Field of The Invention
This invention relates to antiarrhythmic compositions. Specifically, this invention relates to certain members of the family of 3,7-diazabicyclo[3.3.1]nonanes and highly selected derivatives thereof. 2. Description of the Prior Art
3-Azabicyclo[3.3.1]nonanes (3-ABN), 3,7-diazabicyclo[3.3.1]nonanes (3,7-DBCN), and certain derivatives thereof are known and have been documented in the literature in two reviews. These reviews are: (a) Chemical Reviews, Volume 81, No. 2, pages 149-174 (1981), entitled "Chemistry of 3-Azabicyclo[3.3.1]nonanes" by R. Jeyaraman and S. Avila and (b) Topics in Stereochemistry, Volume 20, E. L. Eliel and S. H. Wilen, Eds., Interscience-Wiley, Publishers, New York, Chapter entitled "Conformational Analysis of Bicyclo[3.3.1]nonanes and Their Hetero Analogs" by N. S. Zefirov and V. A. Palyulin, 1990. These reviews cover synthesis, reactions and certain aspects of the stereochemistry of such systems. These reviews also acknowledge that there is resemblance of the title compounds to aza- and diazaadamantanes in conformation and stereochemistry and that such systems have been obtained by Mannich reactions involving the condensations of certain ketones with a primary amine.
According to the chemical literature, some derivatives of 3-ABN and 3,7-DBCN have exhibited useful biological properties including analgesic, antiangina, antitussive, antipyretic, and antiarrhythmic agent (AAA) activity. In U.S. Pat. Nos. 4,581,361; 4,778,892; 4,910,311; 4,980,468; 5,043,445; 5,084,572; and 5, 110,933, for example, such materials are disclosed and claimed as antiarrhythmic agents.
The potential use of multi-class action antiarrhythmic agents [classification of action of antiarrhythmic agents has been made; see E. M. Vaughn Williams, "A Classification of Antiarrhythmic Drugs Reassessed After a Decade of New Drugs", Journal of Clinical Pharmacology, Volume 24, pages 129-147 (1984)] is now recognized. The few agents with some multi-class action have also been reviewed in "Cardiovascular Drugs", James A. Bristol, Ed., Wiley-Interscience Publishers, New York, 1986; chapter 2 entitled "Screening Methods and Test Models for Evaluation of Cardioactive Drugs", by Robert J. Lee, Richard J. Gorczynski, and Robert D. E. Reynolds. See also chapter 7 in this reference entitled "Antiarrhythmic Agents" which is authored by Johannes Hartenstein and Bernd Wagner.
Specifically, this invention is related to the above derivatives of 3,7-DBCN [1-46] and precursors [47-100,108-112] thereof for controlling life-threatening arrhythmias associated with the "sudden death syndrome" with individuals who experience heart attacks caused by coronary heart disease. The objective of the present invention is to provide useful compositions that display multi-class antiarrhythmic agent (AAA) activity. Fulfillment of this object and the presence and fulfillment of other objects will be apparent upon complete reading of the specifications and claims herein. The novelty of the invention lies in the the non-predictable, multi-class AAA activity induced by very special substituents in the compositions.